Rodenhuis S, Mulder N H, Sleijfer D T, Koops H S, van de Grampel J C
Cancer Chemother Pharmacol. 1983;10(3):178-81. doi: 10.1007/BF00255757.
(NPAz2)2NSOAz ('SOAz') is the first of a new class of cytotoxic agents containing an inorganic heterocyclic ring system to enter clinical trial. It was used to treat 31 patients with advanced cancer by IV infusion over 30 min on days 1, 2, 3, and 4 of a 21-day cycle, which was postponed if necessary to allow for hematological recovery. A total of 46 courses evaluable for toxicity was given and the tumor response was evaluable in 21 patients. Seven dose levels, ranging from 25 mg/m2 to 300 mg/m2, were studied, with three to six patients at each level. The only major toxicity was myelosuppression, especially thrombocytopenia, which was dose-limiting. Platelets decreased from the 14th day onward, with a nadir 4-5 weeks after administration. Leukopenia was less predictable and reached a nadir 3-5 weeks after administration. In most patients recovery was complete after 6-9 weeks. Myelosuppression was clearly cumulative in succeeding courses and proved irreversible in three patients. Anemia also occurred, but otherwise SOAz was remarkably well tolerated. There were no responses and no therapy-related deaths. The highest tolerated dose for patients who had received no or only minor chemotherapy prior to treatment with SOAz was 300 mg/m2, and that for heavily pretreated patients, 175 mg/m2. Because of cumulative myelotoxicity phase II studies with SOAz are not recommended.
（NPAz2）2NSOAz（“SOAz”）是进入临床试验的一类含有无机杂环系统的新型细胞毒性药物中的首个药物。在21天周期的第1、2、3和4天，通过静脉输注30分钟对31例晚期癌症患者进行治疗，如有必要可推迟以等待血液学恢复。共给予46个可评估毒性的疗程，21例患者可评估肿瘤反应。研究了7个剂量水平，范围从25mg/m2至300mg/m2，每个水平有3至6例患者。唯一的主要毒性是骨髓抑制，尤其是血小板减少，这是剂量限制性的。血小板从第14天开始下降，给药后4 - 5周达到最低点。白细胞减少较难预测，给药后3 - 5周达到最低点。大多数患者在6 - 9周后完全恢复。骨髓抑制在后续疗程中明显累积，3例患者中证明是不可逆的。贫血也会发生，但除此之外SOAz耐受性良好。没有观察到缓解情况，也没有与治疗相关的死亡。在接受SOAz治疗前未接受化疗或仅接受轻微化疗的患者中，最高耐受剂量为300mg/m²；对于预处理严重的患者，最高耐受剂量为175mg/m²。由于累积的骨髓毒性，不建议进行SOAz的II期研究。
